INHIBITION OF NA K ATPASE FROM RAT AORTA BY 2 NA/K PUMP INHIBITORS, OUABAIN AND MARINOBUFAGENIN - EVIDENCE OF INTERACTION WITH DIFFERENT ALPHA-SUBUNIT ISOFORMS/

Recently, we have shown that mammalian plasma cross-reacts with an ant ibody to a bufodienolide Na/K ATPase inhibitor, marinobufagenin. In ra t aorta, marinobufagenin induced vasoconstriction via inhibition of th e vascular smooth muscle Na/K pump, whereas ouabain had its predominan t effect on pumps localized to nerve endings. Na/K ATPase inhibitory e ffects of ouabain and marinobufagenin were studied in two membrane fra ctions isolated from Fisher 344xBN rat thoracic aorta by sucrose densi ty gradient centrifugation. One fraction contained predominantly the a lpha-3 isoform of Na/K ATPase and represented membranes from the periv ascular nerve endings (neuronal plasmalemma). The other membrane fract ion, containing predominantly the alpha-1 isoform, was derived from th e vascular smooth muscle sarcolemma. The IC50 for inhibition of the Na /K ATPase by ouabain and marinobufagenin were 2.6 nmol/L and 0.14 mu m ol/L in the neuronal plasmalemma, and 50 nmol/L and 2.1 nmol/L in sarc olemma, respectively. These results confirm the view that differential responsiveness to endogenous digitalis-like factors is a functional f eature of alpha isoforms of Na/K ATPase. (C) 1997 American Journal of Hypertension, Ltd.